Method for applying a coating to a medical device

ABSTRACT

This invention provides a method for efficiently applying a coating to each of a plurality of objects selected from the group consisting of ophthalmic lenses, molds for making ophthalmic lenses, and other medical devices, the method comprising dipping the plurality of objects into a coating bath containing a coating solution having a coating material; and creating with a means a convective current flow and thereby forcing a coating solution flowing over and under each of the plurality of ophthalmic lenses. In a preferred embodiment, the plurality of objects are held in baskets which are pre-conditioned to have a first layer of polyelectrolytes and a second layer of aqueous solution or have a mixed layer of polyelectrolytes and aqueous solution on the surfaces of the baskets.

This invention relates to a method of applying efficiently a uniformcoating to an object, especially to an ophthalmic lens or to a mold formaking an ophthalmic lens.

BACKGROUND

Many devices used in biomedical applications require that the bulk ofthe device have one property, while the surface of the device hasanother property. For example, contact lenses may have high oxygenpermeability through the lens to maintain good corneal health. However,materials that exhibit exceptionally high oxygen permeability (e.g.polysiloxanes) are typically hydrophobic and will adhere to the eye.Thus, a contact lens generally has a core or bulk material that ishighly oxygen permeable and hydrophobic, and a surface that has beentreated or coated to increase hydrophilic properties, thereby allowingthe lens to freely move on the eye without adhering excessive amounts oftear lipid and protein.

In order to modify the hydrophilic nature of a relatively hydrophobiccontact lens material, a coating may be applied onto the surface of acontact lens using a number of technologies, including a plasmatreatment process, a Langmuir-Blodgett deposition process, a controlledspin casting process, a chemisorption process, a vapor deposition and alayer-by-layer polymer adsorption process. The layer-by-layer polymeradsorption (LbL) process could be one useful process for increasinghydrophilic properties of contact lenses. The prior art teaches that anarticle having hydrophilic surfaces can be coated using a LbL process,where the article having hydrophilic surfaces is dipped in apolyelectrolyte solution (e.g., polycations such as polyallylamine orpolyethyleneimine). However, the prior art teaches that, prior todipping, the surfaces of the article are treated in order to createsurfaces having an affinity for the polyelectrolyte.

It was unexpectedly discovered by some of us that a LbL process can beused in coating hydrophobic contact lenses in dry or wet state withoutany pretreatment (WO9935520). By dipping iteratively lenses in analternating fashion to a polyanion (e.g., polyacrylic acid, PAA)solution and a polycation (polyallylamine hydrochloride, PAH) solution,a hydrophilic surface can be coated onto the lenses.

During a LbL process, each of a plurality of lenses is generally held ina lens carrying cage which comprises a male and female basket halves.Many of such cages can be affixed together to form trays of baskets.Such trays may then be placed side-by-side to allow hundreds orthousands of lenses being simultaneously processed with a coatingsolution. However, there are several problems associated with the LbLcoating processes, which could affect the quality of coatings on lenses.One problem is the adhesion of lenses to baskets which hold them. Sincelens-holding baskets and/or trays generally have hydrophobic surfaces,lenses have a tendency to adhere on the baskets due tohydrophobic-hydrophobic interactions. This can affect the uniformity andcompleteness of coatings on lenses. In addition, when bubbles are formedin a coating solution, they tends to adhere to baskets and/or trays.Under such circumstance, bubbles can prevent a LbL solution fromreaching the surfaces of lenses and result in bubble-defect in the lenscoating. Therefore, there is a great need for developing methods andsystems for efficiently coating a uniform hydrophilic coat to contactlenses.

Furthermore, when an aqueous LbL coating process is employed to modifythe hydrophilic nature of a relatively hydrophobic contact lensmaterial, microorganisms may grow in an aqueous coating solution andproduce toxins (exotoxins or endotoxins) that may lead to physiologicalirritation or mammalian cell death. Such bioburden problem may beprevented by using antibiotics. However, widely using of antibioticswould lead to the proliferation of antibiotics-resistant bacteria.Therefore, there is need for a LbL coating process having a minimizedbioburden level.

An object of the invention is to provide a method and system forapplying a uniform liquid coating to an ophthalmic lens or a mold usedto produce the ophthalmic lens.

Another object of the invention is to provide a LbL coating processhaving a minimized bioburden level.

SUMMARY OF THE INVENTION

In one aspect of the invention, a method of efficiently applying acoating to each of a plurality of objects comprises dipping theplurality of objects into a bath containing a coating solutioncontaining a coating material and stirring the coating solution with astirring means or agitating the plurality of the objects in the bathwith an agitating means, thereby minimizing the formation ofconcentration gradients of the coating material in the coating solutionaround each of the plurality of objects.

In another aspect of the invention, a system for efficiently applying acoating to each of a plurality of objects comprises one or more trayseach comprising a plurality of baskets, each of which is capable ofholding one of the plurality of objects and a coating solution bathcontaining a stirring means for stirring the coating solution orcontaining an agitating means for agitating the trays or containingcombination of both, wherein the stirring means or the agitating meansor the combination of both are capable of minimizing the formation ofconcentration gradients of a coating material in the coating solutionaround each of the plurality of objects.

In still another aspect of the invention, a method for efficientlyapplying a coating to each of a plurality of objects comprisespre-conditioning a plurality of baskets, loading each of the pluralityof objects into one of the plurality of the pre-conditioned baskets, anddipping the plurality of objects into a bath containing a coatingsolution having a coating material.

In a further aspect of the invention, a LbL coating process, in whichthe level of bioburden is minimized, comprises dipping a plurality ofobjects into a coating solution having a pH value of about 2 to 6.5,wherein the coating solution is contained in a disposable plastic linerwhich is placed in a container and wherein the liner is discarded afteruse for up to 24 hours.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In one aspect, the present invention provides a method for efficientlyapplying a coating to each of a plurality of objects comprises dippingthe plurality of objects into a bath containing a coating solutionhaving a coating material and stirring the coating solution with astirring means or agitating the plurality of objects in the bath with anagitating means, thereby minimizing the formation of concentrationgradients of the coating material in the coating solution around each ofthe plurality of objects. The temperature of the coating solution ispreferably 14° C.-30° C., more, preferably 16°C.-25° C. A person skilledin the art will know how to control the temperature of a coatingsolution.

In a preferred embodiment, the method for efficiently applying a coatingto each of a plurality of objects comprises an additional step ofremoving the plurality of objects from the bath by a removing means ormanually. In a further preferred embodiment, the method for efficientlyapplying a coating to each of a plurality of objects further comprises astep of loading manually or with a loading means each of the pluralityof objects into one of baskets before the dipping step and/or a step ofunloading manually or with the loading means each of the plurality ofobjects out of the baskets.

“An object” refers to an ophthalmic lens, a mold for making anophthalmic lens, or a medical device other than ophthalmic lens.

“A medical device” as used herein refers to a device having surfacesthat contact tissue, blood, or other bodily fluids of patients in thecourse of their operation. Exemplary medical devices include: (1)extracorporeal devices for use in surgery such as blood oxygenators,blood pumps, blood sensors, tubing used to carry blood and the likewhich contact blood which is then returned to the patient; (2)prostheses implanted in a human or animal body such as vascular grafts,stents, pacemaker leads, heart valves, and the like that are implantedin blood vessels or in the heart; (3) devices for temporaryintravascular use such as catheters, guide wires, and the like which areplaced into blood vessels or the heart for purposes of monitoring orrepair; and (4) ophthalmic lenses.

“An ophthalmic lens”, as used herein, refers to a contact lens (hard orsoft), or an intraocular lens.

“A coating material” refers to a polymer material that can change thehydrophilic properties of the surface of an object. Exemplary coatingmaterials are polyelectrolytes.

Any known, suitable stirring means can be used in the invention.Preferably, the stirring means is capable of creating a convectivecurrent flow and thereby forcing a coating solution flowing over andunder each of a plurality of objects to be coated. In this preferredembodiment, the coating solution is constantly mixed and each of theplurality of objects are completely enveloped by a well-mixed coatingsolution. Therefore, the coating process can be highly efficient.

An exemplary stirring means for creating a convective current flow inthe coating bath is an open or closed pumping system that may beattached to a plenum. The plenum is capable of allowing the coatingsolution to be evenly distributed over each of the plurality of objects.

Any known, suitable agitating means can be used in the invention.Preferably, the agitating means is capable of moving a tray containing aplurality of objects in a linear fashion in the coating bath. In thispreferred embodiment, a coating solution in the coating bath is stagnantwhile the plurality of objects are mechanically moved through thecoating solution, thus forcing the coating solution to flow over andunder each of the plurality of objects. The coating process according tothis embodiment can be highly efficient because the coating solution cancompletely envelop each of the plurality of objects while it is mixed.

“A tray” refers to a flat device that comprises or carries a pluralityof baskets. Trays can be made from any materials that are compatiblewith a coating solution.

“A basket” refers to an object holding device having a first and asecond halves, each of which has openings which allows a fluid to passthrough the basket while the object is in place. Generally, baskets aremade of a plastic but it can be made of any easily fabricated material.The shape of a basket can be designed to accommodate the shape of anobject to be held. Preferably, a basket has a lattice network structureand has a percentage of opening surface over total surface being atleast 25%.

Any known, suitable removing means can be used to remove the pluralityof objects. An exemplary removing means is a robotic arm which iscapable of picking up trays containing the plurality of objects undercontrol of a computer system.

A person skilled in the art can select a known, suitable loading meansfor loading each of the plurality of objects into one of baskets in atray or unloading the object out of the baskets. An example of loadingmeans is an air-assisted device that is capable of picking and holdingan ophthalmic lens under a negative pressure and of releasing the lensunder an even or positive pressure. Loading and/or unloading ofophthalmic lenses can be carried out one lens at one time or preferablymore than two lens at one time. Preferably, the loading and/or unloadingprocesses can be carried out automatically under control of a computersystem.

In another aspect, the present invention provides a system forefficiently applying a coating to each of a plurality of objectscomprises a tray comprising a plurality of baskets, each of which iscapable of holding one of the plurality of objects and a coatingsolution bath containing a stirring means for stirring the coatingsolution or containing an agitating means for agitating the tray orcontaining combination of both, wherein the stirring means or theagitating means or the combination of both are capable of minimizing theformation of concentration gradients of a coating material in thecoating solution around each of the plurality of objects. In alternativepreferred embodiments, the stirring means is capable of creating aconvective current flow and thereby forcing a coating solution flowingover and under each of a plurality of objects to be coated, and/or theagitating means is capable of moving a tray containing a plurality ofobjects in a linear fashion in the coating bath. In a further preferredembodiment, the system of the invention further comprises a removingmeans for removing the object from the coating bath and/or a loadingmeans for loading each of the objects into one of baskets in a tray orfor unloading the objects from the baskets.

An exemplary preferred stirring means is an open or closed pumpingsystem that may be attached to a plenum which capable of allowing thecoating solution to be evenly distributed over each of the plurality ofobjects.

In still another aspect, the present invention provides a method forefficiently applying a coating to each of a plurality of objectscomprises pre-conditioning a plurality of baskets which are contained inone or more trays, loading each of the plurality of objects into one ofthe plurality of the pre-conditioned baskets, and dipping the pluralityof objects into a bath containing a coating solution having a coatingmaterial. The temperature of the coating solution is preferably about14° C.-30° C., more preferably about 16° C.-25° C.

“Pre-conditioning a plurality of baskets” refers to one or moreprocesses that improve permanently or temporally the hydrophilicproperties of the surfaces of the plurality of baskets and forms anaqueous layer covering the surfaces of the plurality of baskets.

The hydrophilic properties of the surfaces of the plurality of basketscan be improved permanently by forming a layer of hydrophilic polymermaterials. The formation of such layer on baskets can be achieved byusing one or more technologies selected from the group consisting of aplasma treatment process, a Langmuir-Blodgett deposition process, acontrolled spin casting process, a chemisorption process, a vapordeposition and a layer-by-layer polymer adsorption (LbL coating)process. For example, baskets can be coated with a layer of hydrophilicpolymer materials (e.g., polyelectrolytes) by using a LbL coatingprocess with a conditioning solution or first by plasma treatment andsubsequent by LbL coating with a conditioning solution. The layer ofhydrophilic polymer materials on the surfaces of the baskets canfacilitate retaining of an aqueous layer, which can serve as a blanketseparating objects from the hydrophobic surfaces of the baskets. Theaqueous layer can still allow polyelectrolytes in a LbL coating solutionto reach the surfaces of objects in soft contact via the aqueous layerwith baskets, because of diffusion of polyelectrolytes in the coatingsolution.

The hydrophilic polymer material in the conditioning solution can be acoating material which is used in the coating of objects, or can be anypolymer material other than the coating material used in coatingobjects.

Alternatively, the pre-conditioning of baskets can be carried out asfollows. Objects may be placed into one of the two halves of the basketswhile a tray containing those halves are being conditioned in aconditioning solution. This allows the objects and the tray to be eithersimultaneously or sequentially conditioned so that both have anon-interactive, hydrophilic surface and an aqueous layer is formedbetween the surfaces of objects and of the baskets.

Advantages of pre-conditioning of baskets and/or trays are (1)minimizing the interactions between the uncoated surfaces of objects andthe surfaces of baskets and (2) preventing bubble formation or bubbleadhesion to the baskets and/or tray.

Trays which comprises preconditioned baskets which hold a pluralityobjects then can be queued in the same conditioning solution awaitingfurther processing. Such queue may provide production versatilitywithout degradation to the objects or the surfaces of the objects sincethe potential for the objects to stick to baskets is minimized.

In a further preferred embodiment, full-loaded trays, as they are beingprocessed in a LbL production environment, are place in a way that allobjects are mounted vertically. This allows the objects to drain quicklyand efficiently and thereby to minimize solution carry-over into thenext LbL coating solution.

In a more preferred embodiment, the coating solution is stirred with astirring means and/or the trays containing the plurality of objects areagitated in the bath with an agitating means, thereby minimizing theformation of concentration gradients of the coating material in thecoating solution around each of the plurality of objects and allowingthe coating solution to pass over all surfaces of the objects equally.The stirring means is capable of creating a convective current flow andthereby forcing a coating solution flowing over and under each of aplurality of objects to be coated. Preferably, the stirring means is anopen or closed pumping system that may be attached to a plenum whichcapable of allowing the coating solution to be evenly distributed overeach of the plurality of objects. The agitating means is capable ofmoving a tray containing a plurality of objects in a linear fashion inthe coating bath.

The methods and systems of the invention can be used to apply a coatingto a mold used in forming ophthalmic lenses and thereafter forming anophthalmic lens within the mold such the ophthalmic lens becomes coatedwith materials contained in a coating solution.

In general, a mold can be formed by any method known in the art, such asby injection molding. Typically, two mold halves are formed and laterjoined together such that a cavity can form therebetween. Although it istypically desired that the mold be made from a material having at leastsome affinity to polyionic materials, virtually all materials known inthe art for making molds can be used. For example, various types ofthermoplastic material, such as UV-transmissive or UV-opaquethermoplastic materials, can be utilized to form a mold of the presentinvention. In one embodiment, one portion of the mold is formed from aUV transmissive material, such as polymethylacrylate, so that UV lightcan later pass through the section to cure a polymerizable materialdispensed within the mold. In another embodiment, another portion of themold is formed from a UV-opaque material that blocks UV light.

Once a mold is formed, various coating materials and/or additives can beapplied thereon.

The methods and apparatus of the invention also can be used to apply acoating to a medical device to modify its surface properties andfunctions.

In a further aspect, the present invention provides a LbL coatingprocess, in which the level of bioburden is minimized, the processcomprising dipping a plurality of objects into a coating solution havinga pH value of about 2 to 6.5, preferably about 2.5 to 4.5, wherein thecoating solution is contained in a disposable plastic liner which isplaced in a container and wherein the liner is discarded after use forup to 24 hours.

By using a disposable plastic liner, any biofilm that may have formed onthe liner can be removed together with the discarding of the liner.

It has been discovered that when a coating solution has a pH lower than3, no significant build-up of bioburden level in the coating solutioncan be observed for a period of time up to one week. It has also beendiscovered that a coating solution has a pH of about 2.5 to 4.5, nosignificant build-up of bioburden level in the coating solution can beobserved for a period of time up to three days.

Advantage of the LbL coating process of the invention is to cut theproduction cost of a LbL coating process. There is no need for preparingfrequently coating solutions and for incorporating antibiotics incoating solutions.

1-19. (canceled)
 20. A system for efficiently applying a coating to eachof a plurality of objects, the system comprising: 1) One or more trayseach comprising a plurality of baskets, each of which is capable ofholding one of the plurality of objects; and 2) a coating solution bathcontaining a stirring means for stirring the coating solution orcontaining an agitating means for agitating the trays or containingcombination of both, wherein the stirring means or the agitating meansor the combination of both are capable of minimizing the formation ofconcentration gradients of a coating material in the coating solutionaround each of the plurality of ophthalmic lenses
 21. A system of claim20, wherein the objects are selected from the group consisting ofophthalmic lenses, molds for making ophthalmic lenses, and medicaldevices other than ophthalmic lenses.
 22. A system of claim 21, whereinthe baskets are pre-conditioned to have a first layer ofpolyelectrolytes and a second layer of aqueous solution or have a mixedlayer of polyelectrolytes and aqueous solution on the surfaces ofbaskets.
 23. A system of claim 22, wherein the coating bath comprises astirring means capable of creating a convective current flow and therebyforcing a coating solution flowing over and under each of the pluralityof objects.
 24. A system of claim 23, wherein the stirring means is anopen or closed pumping system attached to a plenum capable of allowingthe coating solution to be evenly distributed over each of the pluralityof objects.
 25. A system of claim 22, wherein the agitating means iscapable of moving the trays containing the plurality of objects in alinear fashion in the coating bath.
 26. A system of claim 22, whereinthe system further comprises a temperature controlling means forcontrolling the temperature of the coating solution.
 27. A system ofclaim 26, wherein the system further comprises a removing means forremoving the plurality of baskets and/or a loading means for loadingeach of the plurality of objects into one of the plurality of baskets orfor unloading the plurality of objects out of the plurality of baskets.28-38. (canceled)
 39. A LbL coating process, in which the level ofbioburden is minimized, the process comprising dipping a plurality oflenses into a coating solution having a pH value of about 2 to 6.5,wherein the coating solution is contained in a disposable plastic linerwhich is placed in a container and wherein the liner is discarded afteruse for up to 24 hours.
 40. A LbL coating process, wherein the coatingsolution has a pH value of about 2.5 to 4.5.